期刊
CANCER LETTERS
卷 374, 期 2, 页码 315-323出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.02.021
关键词
TRIM16; TDP43; Neuroblastoma; Breast cancer; Yeast two-hybrid assay
类别
资金
- National Health and Medical Research Council Australia [APP1016699]
- Cancer Institute NSW [14/TPG/1-13]
- Cancer Council NSW [PG11-06]
- Australia Postgraduate Research Award, UNSW
Tripartite Motif-containing protein 16 (TRIM16) is a member of a large family of tripartite motif (TRIM) proteins, that has been implicated in the pathogenesis of multiple cancers. However, the mechanism by which TRIM16 acts as a tumour suppressor is currently unknown. We used the versatile yeast two hybrid assay on a cDNA library from human testes, which has relative high TRIM16 expression, to identify potential TRIM16-binding proteins. We identified transactive response DNA-binding protein 43 (TDP43) as a novel TRIM16 binding protein. Co-immunoprecipitation assay demonstrated that TDP43 bound TRIM16 in neuroblastoma and breast cancer cells. Enforced over-expression of TRIM16 increased the protein half-life of TDP43, through the inhibition of the proteosomal degradation pathway. High levels of TRIM16 and TDP43 are associated with good prognosis in both human neuroblastoma and breast cancer tissues. Importantly, we found TDP43 expression was required for TRIM16-induced inhibition of neuroblastoma and breast cancer cell growth and the repressive effect of TRIM16 on cell cycle regulatory proteins, E2F1 and pRb. Taken together, our data suggest that TRIM16 and TDP43 are both good prognosis indicators; also we showed that TRIM16 inhibits cancer cell viability by a novel mechanism involving interaction and stabilisation of TDP43 with consequent effects on E2F1 and pRb proteins. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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